In the central nervous system (CNS) myelin is the product of a single cell type, the oligodendrocyte. Prior to myelin production, oligodendrocytes coordinately express several myelin-specific structural proteins. Proteolipid protein (PLP) is the major protein of CNS myelin and its expression is regulated predominantly at the level of transcript ion as a part of the coordinate regulation of myelin genes expression. Analysis of the PLP promoter region, both in vivo in transgenic mice and in vitro in transient transfections studies in tumor cell lines, has only partially elucidated the sequences that control tissue specific expression of PLP in the oligodendrocytes. In my preliminary data I have shown that 16OO bp of PLP promoter sequences are sufficient to support oligodendrocyte-specific PLP expression. These sequences do not support PLP expression in non- oligodendrocyte cells suggesting that an important PLP regulatory element is present in this region. in the current proposal, I plan to identify the DNA sequences that control the oligodendrocyte-specific PLP expression, to identify and analyze the sequence-specific binding factors that interact with these regulatory sequences. Finally, l will begin to isolate cDNA encoding the PLP enhancer binding protein.